Periodontal disease is a chronic inflammatory condition that may have a significant, negative impact on systemic conditions such as diabetes and cardiovascular disease, and may increase the incidence of preterm birth in pregnant women. Preliminary studies have suggested that controlling oral infection and inflammation may have beneficial systemic effects. Our previous studies have demonstrated that combining traditional, non-surgical periodontal therapy with supplemental, systemically delivered, anti-inflammatory agents provides improved clinical treatment outcomes and at the same time demonstrates a significant impact on systemic markers of inflammation. Studies have shown that many well-recognized disorders are associated with excessive intake of dietary fat, including obesity, insulin resistance, coronary heart disease, and some forms of cancer. While intake of saturated, trans, and arachidonic fatty acids (AA) has been linked to the development of chronic disease, research shows n-3 [polyunsaturated fatty acids (n-3 PUFA)] fatty acids, specifically fish oils (eg. cold-water fish such as salmon, cod, tuna, or mackerel) or plant oils (eg. flax, linseed), can contribute to the prevention and treatment of disease. Dietary n-3 PUFA provides a benefit by reducing inflammation and improving antibacterial and autoimmune responses in many chronic inflammatory medical conditions. It is hypothesized that the use of n-3 PUFA as a dietary supplement, could have an important impact systemic health by reducing chronic periodontal disease and systemic inflammation either alone or when combined with periodontal therapy. This proposal will study the effects of dietary n-3 PUFA capsules (1000 mg t.i.d) compared to placebo (safflower oil capsules; t.i.d) in 200 subjects with generalized periodontitis, a condition known to have negative systemic outcomes and be associated with a hyper-inflammatory phenotype as demonstrated by elevated inflammatory cell function and elevated systemic levels of C-reactive protein. Using a randomized, double blind, placebo controlled intervention study of 4 groups (5o subjects/group), we will study the effects of combining n-3 PUFA or placebo with oral hygiene or sealing and root planing on systemic inflammation (aim 1; primary outcome = CRP; secondary outcome: other acute phase reactants); periodontal inflammation and clinical outcomes (aim 2; primary outcome = clinical measures; secondary outcome: inflammatory mediators in gingival crevicular fluid) and bacterial colonization of plaque (aim 3; primary outcome: changes in levels of P. gingivalis, T. denticola, and T.forsythensis). If this study demonstrates that dietary supplementation with n-3 PUFA has significant benefits for oral and systemic health, it will have enormous public health implications for providing a cost effective decrease in the risk for negative outcomes of systemic conditions frequently associated with oral disease.